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Gupta R.K.,University College London | Gupta R.K.,Public Health England | Rice B.,Public Health England | Brown A.E.,Public Health England | And 11 more authors.
The Lancet HIV | Year: 2015

Background Whether the incidence of tuberculosis in HIV-positive people receiving long-term antiretroviral therapy (ART) remains above background population rates is unclear. We compared tuberculosis incidence in people receiving ART with background rates in England, Wales, and Northern Ireland. Methods We analysed a national cohort of HIV-positive individuals linked to the national tuberculosis register. Tuberculosis incidence in the HIV-positive cohort (2007-11) was stratifi ed by ethnic origin and time on ART and compared with background rates (2009). Ethnic groups were defi ned as follows: the black African group included all individuals of black African origin, including those born in the UK and overseas; the white ethnic group included all white individuals born in the UK and overseas; the south Asian group included those of Indian, Pakistani, and Bangladeshi origin, born in the UK and overseas; and the other ethnic group included all other ethnic origins, including black Afro-Caribbeans. Findings The HIV-positive cohort comprised 79 919 individuals, in whom there were 1550 incident cases in 231 664 person-years of observation (incidence 6·7 cases per 1000 person-years). Incidence of tuberculosis in the HIVpositive cohort was 13·6 per 1000 person-years in black Africans and 1·7 per 1000 person-years in white individuals. Incidence of tuberculosis during long-term ART (≥5 years) in black Africans with HIV was 2·4 per 1000 personyears, similar to background rates of 1·9 per 1000 person-years in this group (rate ratio 1·2, 95% CI 0·96-1·6; p=0·083); but in white individuals with HIV on long-term ART the incidence of 0·5 per 1000 person-years was higher than the background rate of 0·04 per 1000 person-years (rate ratio 14·5, 9·4-21·3; p<0·0001). The increased incidence relative to background in white HIV-positive individuals persisted when analysis was restricted to person-time accrued on ART with CD4 counts of at least 500 cells per μL and when white HIV-positive individuals born abroad were excluded. Interpretation Tuberculosis incidence is unacceptably high irrespective of HIV status in black Africans. In white individuals with HIV, tuberculosis incidence is signifi cantly higher than background rates in white people despite long-term ART. Expanded testing and treatment for latent tuberculosis infection to all HIV-infected adults, irrespective of ART status and CD4 cell count, might be warranted. Funding Public Health England.


Zenner D.,Public Health England | Abubakar I.,Public Health England | Conti S.,Public Health England | Gupta R.K.,University College London | And 8 more authors.
Thorax | Year: 2015

Introduction The impact of TB disease on survival in people living with HIV in high resource settings is not well documented in the antiretroviral treatment (ART) era. We calculated TB incidence rates and compared the mortality of persons with and without HIV-TB in a UK HIV cohort in the post-ART era, to determine the impact of HIV-TB on survival in the UK. Methods We linked the national cohort of persons (aged ≥15 years) diagnosed with HIV between 2000 and 2008 in England, Wales and Northern Ireland with the national TB register and deaths from the Office of National Statistics. We compared all-cause and AIDS-specific mortality in patients with and without TB by estimating HRs using Cox regression modelling allowing for potential predictors. Results Overall, 3188 (7.2%) individuals developed TB infection among a cohort of 44 050 HIV-diagnosed persons and 149 663 person-years. The cumulative TB incidence rate was 2.13 per 100 person-years with a spike within the first 6 months after HIV diagnosis. TB coinfected patients comprised 18% of the 1880 deaths during follow-up and 79% of deaths (n=967) in the year following HIV diagnosis. TB coinfection (HR 4.77, 95% CI 4.11 to 5.54) was significantly associated with increased all-cause mortality. Analysis of AIDS-related survival showed similar results. Discussion The unexpected high mortality in patients with HIV-TB in a population with good healthcare access and ART availability highlights the importance of improving active and latent TB case-finding among patients with HIV, and HIV-testing among patients with TB, to ensure appropriate and prompt treatment initiation for both diseases. © 2015 BMJ Publishing Group Ltd & British Thoracic Society.


Zenner D.,Public Health England | Zenner D.,University College London | Abubakar I.,Public Health England | Abubakar I.,University College London | And 10 more authors.
Thorax | Year: 2015

Introduction: The impact of TB disease on survival in people living with HIV in high resource settings is not well documented in the antiretroviral treatment (ART) era. We calculated TB incidence rates and compared the mortality of persons with and without HIV-TB in a UK HIV cohort in the post-ART era, to determine the impact of HIV-TB on survival in the UK. Methods: We linked the national cohort of persons (aged ≥15 years) diagnosed with HIV between 2000 and 2008 in England, Wales and Northern Ireland with the national TB register and deaths from the Office of National Statistics. We compared all-cause and AIDS-specific mortality in patients with and without TB by estimating HRs using Cox regression modelling allowing for potential predictors. Results: Overall, 3188 (7.2%) individuals developed TB infection among a cohort of 44 050 HIV-diagnosed persons and 149 663 person-years. The cumulative TB incidence rate was 2.13 per 100 person-years with a spike within the first 6 months after HIV diagnosis. TB coinfected patients comprised 18% of the 1880 deaths during follow-up and 79% of deaths (n=967) in the year following HIV diagnosis. TB coinfection (HR 4.77, 95% CI 4.11 to 5.54) was significantly associated with increased all-cause mortality. Analysis of AIDS-related survival showed similar results. Discussion: The unexpected high mortality in patients with HIV-TB in a population with good healthcare access and ART availability highlights the importance of improving active and latent TB case-finding among patients with HIV, and HIV-testing among patients with TB, to ensure appropriate and prompt treatment initiation for both diseases.


Gupta R.K.,Public Health England | Gupta R.K.,University College London | Brown A.E.,Public Health England | Zenner D.,Public Health England | And 8 more authors.
AIDS | Year: 2015

Objective: To investigate whether HIV-infected individuals diagnosed with tuberculosis (HIV-TB) around the time of starting antiretroviral therapy (ART) have impaired CD4 + cell responses to treatment. Design: Analysis of a national cohort of HIV-infected adults, linked to the national TB surveillance system for England, Wales and Northern Ireland, including individuals starting ART from 2005 to 2009. Methods: We compared CD4 + cell responses in HIV-infected individuals starting ART with a TB diagnosis ('HIV-TB cohort') with those not known to have TB ('TB-free cohort'). The TB-free cohort was frequency-matched to the HIV-TB cases for sex, age strata, baseline CD4 + strata and ethnicity. Median change in CD4 + cell count from baseline (ΔCD4 +) was calculated at 6-monthly intervals until 36 months. Results: There were 593 and 1779 individuals in the HIV-TB and TB-free cohorts, respectively (median follow-up 3.8 years). In both cohorts, median age was 36 years, 49.2% were women and 74.9% were black-African. Median baseline CD4 + at the start of treatment was similar in the HIV-TB and TB-free cohorts (74 vs. 80 cells/μl). Median ΔCD4 + was similar in HIV-TB and TB-free cohorts at all time points [294 (inter-quartile range 198-424) cells/μl in HIV-TB cohort; 296 (inter-quartile range 196-431) cells/μl in TB-free cohort after 3 years of ART]. A higher proportion of the HIV-TB cohort than the TB-free cohort died during follow-up (4.2 vs. 2.2%; P = 0.01); 78.5% of all individuals who died had a baseline CD4 + cell count below 100 cells/μl. Conclusions: Long-term CD4 + cell recovery during ART appears similar in HIV-TB and TB-free patients. Significant mortality in both cohorts highlights the need for earlier HIV diagnosis and ART initiation. © 2015 Wolters Kluwer Health, Inc. All rights reserved.

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